壳聚糖基微球在口腔组织病损治疗中的研究进展

doi:10.13591/j.cnki.kqyx.2023.01.016

摘要/Abstract

摘要：

壳聚糖基微球是以壳聚糖为主要材料,通过微球加工技术得到的具有特殊结构的微粒。它具有良好的缓控释药物能力,可提供支架作用,在口腔临床治疗中具有很大的应用前景,但目前仍处于研究阶段,尚未应用于临床。该文就目前国内外对于壳聚糖基微球在口腔颌骨组织缺损、牙周病损、牙体牙髓病变及神经组织损伤治疗方面的研究进展作一综述,为后续研究及最终实现临床应用提供参考。

关键词: 壳聚糖基微球, 载药, 缓释, 口腔组织

Abstract:

Chitosan-based microspheres use chitosan as the main material to obtain particles with special structures through microsphere processing technology. They have the ability of slow and controlled release of drugs and the role of scaffolding, which have great application prospect in stomatology, but the application of chitosan-based microspheres is still in the research stage and has not yet been applied in clinical practice. This article reviews progress of domestic and foreign research on chitosan-based microspheres, in aspects of treatment of oral and jawbone tissue defects, periodontal diseases, dental pulp diseases and nerve tissue injury, in order to provide reference for follow-up research.

Key words: chitosan-based microsphere, drug loading, sustained release, oral tissue

中图分类号:

R780.1

周华俊,丁榆德,杨帆. 壳聚糖基微球在口腔组织病损治疗中的研究进展[J]. 口腔医学, 2023, 43(1): 92-96.

ZHOU Huajun,DING Yude,YANG Fan. Progress of research on chitosan-based microspheres in oral tissue lesions[J]. Stomatology, 2023, 43(1): 92-96.

图/表 1

参考文献 43

[1]	Sarasam AR, Brown P, Khajotia SS, et al. Antibacterial activity of chitosan-based matrices on oral pathogens[J]. J Mater Sci Mater Med, 2008, 19(3):1083-1090. doi: 10.1007/s10856-007-3072-z
[2]	Bi YG, Lin ZT, Deng ST. Fabrication and characterization of hydroxyapatite/sodium alginate/chitosan composite microspheres for drug delivery and bone tissue engineering[J]. Mater Sci Eng C Mater Biol Appl, 2019, 100:576-583. doi: 10.1016/j.msec.2019.03.040
[3]	Pahuja S, Aggarwal S, Sarup P. Formulation and characterization of losartan loaded chitosan microspheres:Effect of crosslinking agents[J]. Drug Res(Stuttg), 2021, 71(4):204-212.
[4]	Zhang N, Zhang HH, Li R, et al. Preparation and adsorption properties of citrate-crosslinked chitosan salt microspheres by microwave assisted method[J]. Int J Biol Macromol, 2020, 152:1146-1156. doi: S0141-8130(19)36021-0 pmid: 31751706
[5]	Zhang ZL, Li LJ, Sun D, et al. Preparation and properties of chitosan-based microspheres by spray drying[J]. Food Sci Nutr, 2020, 8(4):1933-1941. doi: 10.1002/fsn3.1479
[6]	dos Santos BFF, Maciel MA, Tavares A, et al. Synthesis and preparation of chitosan/clay microspheres:Effect of process parameters and clay type[J]. Materials(Basel), 2018, 11(12):2523.
[7]	Oryan A, Sahvieh S. Effectiveness of chitosan scaffold in skin, bone and cartilage healing[J]. Int J Biol Macromol, 2017, 104(Pt A):1003-1011. doi: S0141-8130(17)31371-5 pmid: 28684351
[8]	Rizeq BR, Younes NN, Rasool K, et al. Synthesis, bioapplications, and toxicity evaluation of chitosan-based nanoparticles[J]. Int J Mol Sci, 2019, 20(22):5776. doi: 10.3390/ijms20225776
[9]	El Knidri H, Belaabed R, Addaou A, et al. Extraction, chemical modification and characterization of chitin and chitosan[J]. Int J Biol Macromol, 2018, 120(Pt A):1181-1189. doi: S0141-8130(18)31374-6 pmid: 30172808
[10]	Kim DH, Huegel J, Taylor BL, et al. Biocompatibility and bioactivity of an FGF-loaded microsphere-based bilayer delivery system[J]. Acta Biomater, 2020, 111:341-348. doi: S1742-7061(20)30254-3 pmid: 32428684
[11]	Mikai A, Ono M, Tosa I, et al. BMP-2/β-TCP local delivery for bone regeneration in MRONJ-like mouse model[J]. Int J Mol Sci, 2020, 21(19):7028. doi: 10.3390/ijms21197028
[12]	Teng F, Yu DD, Wei LF, et al. Preclinical application of recombinant human bone morphogenetic protein 2 on bone substitutes for vertical bone augmentation:A systematic review and meta-analysis[J]. J Prosthet Dent, 2019, 122(4):355-363. doi: S0022-3913(18)30829-1 pmid: 30782462
[13]	Xia YJ, Xia H, Chen L, et al. Efficient delivery of recombinant human bone morphogenetic protein(rhBMP-2)with dextran sulfate-chitosan microspheres[J]. Exp Ther Med, 2018, 15(4):3265-3272.
[14]	Xia YJ, Wei W, Xia H, et al. Effect of recombinant human bone morphogenetic protein delivered by chitosan microspheres on ectopic osteogenesis in rats[J]. Exp Ther Med, 2019, 17(5):3891-3898.
[15]	Thangavelu M, Adithan A, John Peter JS, et al. Ginseng compound K incorporated porous Chitosan/biphasic calcium phosphate composite microsphere for bone regeneration[J]. Int J Biol Macromol, 2020, 146:1024-1029. doi: S0141-8130(19)34447-2 pmid: 31726141
[16]	Sobhani A, Rafienia M, Ahmadian M, et al. Fabrication and characterization of polyphosphazene/calcium phosphate scaffolds containing chitosan microspheres for sustained release of bone morphogenetic protein 2 in bone tissue engineering[J]. Tissue Eng Regen Med, 2017, 14(5):525-538. doi: 10.1007/s13770-017-0056-z pmid: 30603507
[17]	Huang D, Niu LL, Li J, et al. Reinforced chitosan membranes by microspheres for guided bone regeneration[J]. J Mech Behav Biomed Mater, 2018, 81:195-201. doi: S1751-6161(18)30273-X pmid: 29529590
[18]	Pufe T, Wildemann B, Petersen W, et al. Quantitative measurement of the splice variants 120 and 164 of the angiogenic peptide vascular endothelial growth factor in the time flow of fracture healing:A study in the rat[J]. Cell Tissue Res, 2002, 309(3):387-392. doi: 10.1007/s00441-002-0605-0
[19]	Niikura T, Hak DJ, Reddi AH. Global gene profiling reveals a downregulation ofBMP gene expression in experimental atrophic nonunions compared to standard healing fractures[J]. J Orthop Res, 2006, 24(7):1463-1471. doi: 10.1002/jor.20182
[20]	Dou DD, Zhou G, Liu HW, et al. Sequential releasing of VEGF and BMP-2 in hydroxyapatite collagen scaffolds for bone tissue engineering:Design and characterization[J]. Int J Biol Macromol, 2019, 123:622-628. doi: S0141-8130(18)32687-4 pmid: 30447364
[21]	Wang B, Booij-Vrieling HE, Bronkhorst EM, et al. Antimicrobial and anti-inflammatory thermo-reversible hydrogel for periodontal delivery[J]. Acta Biomater, 2020, 116:259-267. doi: 10.1016/j.actbio.2020.09.018 pmid: 32937208
[22]	Jepsen K, Jepsen S. Antibiotics/antimicrobials:Systemic and local administration in the therapy of mild to moderately advanced periodontitis[J]. Periodontol 2000, 2016, 71(1):82-112. doi: 10.1111/prd.12121
[23]	Yadav SK, Khan G, Bansal M, et al. Screening of ionically crosslinked chitosan-tripolyphosphate microspheres using Plackett-Burman factorial design for the treatment of intrapocket infections[J]. Drug Dev Ind Pharm, 2017, 43(11):1801-1816. doi: 10.1080/03639045.2017.1349782 pmid: 28673095
[24]	Yadav SK, Khan G, Bonde GV, et al. Design, optimization and characterizations of chitosan fortified calcium alginate microspheres for the controlled delivery of dual drugs[J]. Artif Cells Nanomed Biotechnol, 2018, 46(6):1180-1193. doi: 10.1080/21691401.2017.1366331 pmid: 28830256
[25]	Yoon SW, Kim MJ, Paeng KW, et al. Locally applied slow-release of minocycline microspheres in the treatment of peri-implant mucositis:An experimental in vivo study[J]. Pharmaceutics, 2020, 12(7):668. doi: 10.3390/pharmaceutics12070668
[26]	Yoon SW, Kim MJ, Paeng KW, et al. Efficacy of local minocycline agents in treating peri-implantitis:An experimental in vivo study in beagle dogs[J]. Pharmaceutics, 2020, 12(11):1016. doi: 10.3390/pharmaceutics12111016
[27]	Nuñez J, Vignoletti F, Caffesse RG, et al. Cellular therapy in periodontal regeneration[J]. Periodontol 2000, 2019, 79(1):107-116. doi: 10.1111/prd.12250
[28]	Inanç B, Eser Elçin A, Koç A, et al. Encapsulation and osteoinduction of human periodontal ligament fibroblasts in chitosan-hydroxyapatite microspheres[J]. J Biomed Mater Res, 2007, 82A(4):917-926. doi: 10.1002/jbm.a.31213
[29]	凌均棨, 林家成. 牙髓血运重建术治疗进展[J]. 口腔医学, 2019, 39(10):865-872.
[30]	Jani P, Liu C, Zhang H, et al. The role of bone morphogenetic proteins 2 and 4 in mouse dentinogenesis[J]. Arch Oral Biol, 2018, 90:33-39. doi: S0003-9969(18)30031-1 pmid: 29529483
[31]	Niu XF, Liu ZN, Hu J, et al. Microspheres assembled from chitosan-graft-poly(lactic acid)micelle-like core-shell nanospheres for distinctly controlled release of hydrophobic and hydrophilic biomolecules[J]. Macromol Biosci, 2016, 16(7):1039-1047. doi: 10.1002/mabi.201600020
[32]	Jiang LM, Ayre WN, Melling GE, et al. Liposomes loaded with transforming growth factor β1 promote odontogenic differentiation of dental pulp stem cells[J]. J Dent, 2020, 103:103501. doi: 10.1016/j.jdent.2020.103501
[33]	Li F, Liu X, Zhao SL, et al. Porous chitosan bilayer membrane containing TGF-β1 loaded microspheres for pulp capping and reparative dentin formation in a dog model[J]. Dent Mater, 2014, 30(2):172-181. doi: 10.1016/j.dental.2013.11.005 pmid: 24332410
[34]	Stenberg L, Kodama A, Lindwall-Blom C, et al. Nerve regenera-tion in chitosan conduits and in autologous nerve grafts in healthy and in type 2 diabetic Goto-Kakizaki rats[J]. Eur J Neurosci, 2016, 43(3):463-473. doi: 10.1111/ejn.13068 pmid: 26355640
[35]	张贤平, 王锐英. 神经生长因子(NGF)对周围神经损伤修复的作用[J]. 世界最新医学信息文摘, 2019, 19(86):54-55.
[36]	Zeng W, Huang JH, Hu XY, et al. Ionically cross-linked chitosan microspheres for controlled release of bioactive nerve growth factor[J]. Int J Pharm, 2011, 421(2):283-290. doi: 10.1016/j.ijpharm.2011.10.005
[37]	Zeng W, Rong MY, Hu XY, et al. Incorporation of chitosan microspheres into collagen-chitosan scaffolds for the controlled release of nerve growth factor[J]. PLoS One, 2014, 9(7):e101300. doi: 10.1371/journal.pone.0101300
[38]	Zeng W, Hui H, Liu ZY, et al. TPP ionically cross-linked chitosan/PLGA microspheres for the delivery of NGF for peripheral nerve system repair[J]. Carbohydr Polym, 2021, 258:117684. doi: 10.1016/j.carbpol.2021.117684
[39]	徐弢, 袁玉宇, 林峰, 等. 生物3D打印技术构建神经外科组织修复支架[C]//浙江省医学会神经外科学分会. 2014浙江省神经外科学学术年会论文汇编. 杭州: 浙江省科学技术协会, 2014:2.
[40]	Xiang FF, Wei DQ, Yang YK, et al. Tissue-engineered nerve graft with tetramethylpyrazine for repair of sciatic nerve defects in rats[J]. Neurosci Lett, 2017, 638:114-120. doi: S0304-3940(16)30961-2 pmid: 27988347
[41]	Gao TL, Shi TS, Wiesenfeld-Hallin Z, et al. Sinomenine facilitates the efficacy of gabapentin or ligustrazine hydrochloride in animal models of neuropathic pain[J]. Eur J Pharmacol, 2019, 854:101-108. doi: S0014-2999(19)30228-6 pmid: 30954565
[42]	赵红斌, 刘兴炎, 葛宝丰, 等. 组织诱导性神经导管的制备及性能评价[J]. 生物医学工程学杂志, 2012, 29(2):315-322.
[43]	唐震航, 陈卓. 壳聚糖促进牙釉质仿生矿化修复的研究进展[J]. 口腔医学, 2022, 42(3):256-260.